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Background: Deferasirox (DFX) is used to reduce iron levels in patients with myelodysplastic syndrome (MDS) who develop iron overload after chronic red blood cell infusions. However, DFX can be associated with renal and gastrointestinal toxicities, which may cause treatment interruption or discontinuation. This study aimed to determine the effectiveness and safety of DFX in patients with MDS., Methods: This multicenter, retrospective, observational study was conducted at two hospitals in Italy. Elderly patients with transfusion-dependent MDS received DFX for up to 12 months and were divided into two groups: group A comprised patients who were not under multidisciplinary assessment; group B comprised patients under multidisciplinary control. Treatment effectiveness was estimated by monitoring the serum ferritin (SF) levels throughout the study. Any treatment-related adverse events (AEs), clinically relevant analytical alterations, and reasons for treatment discontinuation were monitored., Results: The study included 44 patients (13 female, 31 male; median age 77.0 years). At 3 months, SF levels decreased by ≥20 % in 29 and 31 % of patients in groups A and B, respectively, in 17 and 36 % of patients at 6 months, and in 22 and 58 % at 12 months. The most common AEs were diarrhea and increased serum creatinine, which were more frequent in group A. The discontinuation rate after renal AE was 15 and 5 % in groups A and B, respectively., Conclusion: Multidisciplinary evaluation can be an effective strategy for monitoring renal function in patients on DFX therapy, to improve treatment adherence and overall efficacy in elderly patients with MDS.

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients., Methods: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed., Results: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively)., Conclusions: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the role of smoking in Barrett's esophagus (BE) and erosive esophagitis (E) compared to endoscopic controls with no BE or E. Smoking is considered a cause of both BE and E, but results on this topic are quite controversial., Methods: Patients with BE (339), E (462) and controls (619: 280 with GERD (gastroesophageal reflux disease)-negative and 339 with GERD-positive anamnesis) were recruited in 12 Italian endoscopy units. Data were obtained from structured questionnaires., Results: Among former smokers, a remarkable upward linear trend was found in BE for all smoking-related predictors. In particular, having smoked for more than 32 years increased the risk more than two times (OR 2.44, 95 % CL 1.33-4.45). When the analysis was performed in the subgroup of subjects with GERD-negative anamnesis, the risk of late quitters (<9 years) passed from OR 2.11 (95 % CL 1.19-3.72) to OR 4.42 (95 % CL 1.52-12.8). A noticeably positive dose-response relationship with duration was seen also among current smokers. As regards E, no straightforward evidence of association was detected, but for an increased risk of late quitters (OR 1.84, 95 % CL 1.14-2.98) in former smokers and for early age at starting (OR 3.63, 95 % CL 1.19-11.1) in GERD-negative current smokers., Conclusions: Smoking seems to be an independent determinant of BE and, to a lesser degree, of E. The elevation in risk is independent from GERD and is already present in light cigarette smokers. Smoking cessation may reduce, but not remove this risk.

Background: Tumour markers are standard tools for the differential diagnosis of cancer. However, the occurrence of nonspecific symptoms and different malignancies involving the same cancer site may lead to a high proportion of misclassifications. Classification accuracy can be improved by combining information from different markers using standard data mining techniques, like Decision Tree (DT), Artificial Neural Network (ANN), and k-Nearest Neighbour (KNN) classifier. Unfortunately, each method suffers from some unavoidable limitations. DT, in general, tends to show a low classification performance, whereas ANN and KNN produce a "black-box" classification that does not provide biological information useful for clinical purposes., Methods: Logic Learning Machine (LLM) is an innovative method of supervised data analysis capable of building classifiers described by a set of intelligible rules including simple conditions in their antecedent part. It is essentially an efficient implementation of the Switching Neural Network model and reaches excellent classification accuracy while keeping low the computational demand. LLM was applied to data from a consecutive cohort of 169 patients admitted for diagnosis to two pulmonary departments in Northern Italy from 2009 to 2011. Patients included 52 malignant pleural mesotheliomas (MPM), 62 pleural metastases (MTX) from other tumours and 55 benign diseases (BD) associated with pleurisies. Concentration of three tumour markers (CEA, CYFRA 21-1 and SMRP) was measured in the pleural fluid of each patient and a cytological examination was also carried out. The performance of LLM and that of three competing methods (DT, KNN and ANN) was assessed by leave-one-out cross-validation., Results: LLM outperformed all other considered methods. Global accuracy was 77.5% for LLM, 72.8% for DT, 54.4% for KNN, and 63.9% for ANN, respectively. In more details, LLM correctly classified 79% of MPM, 66% of MTX and 89% of BD. The corresponding figures for DT were: MPM = 83%, MTX = 55% and BD = 84%; for KNN: MPM = 58%, MTX = 45%, BD = 62%; for ANN: MPM = 71%, MTX = 47%, BD = 76%. Finally, LLM provided classification rules in a very good agreement with a priori knowledge about the biological role of the considered tumour markers., Conclusions: LLM is a new flexible tool potentially useful for the differential diagnosis of pleural mesothelioma.

Background and Objective: Focal endoscopic mucosal resection (EMR) of visible intraepithelial lesions arising within Barrett's esophagus (BE) may miss synchronous lesions that are not endoscopically apparent. Stepwise radical endoscopic resection would obviate this concern by removing all BE; however, it requires repeated endoscopy which may increase the risk of complications, particularly for patients with circumferential BE. The aim of the study was to evaluate the safety and efficacy of one-step complete circumferential resection of BE by cap-assisted EMR (EMR-C) among patients with circumferential BE and high-grade dysplasia or intramucosal carcinoma., Patients and Methods: Between January 2003 and March 2010, 47 patients with circumferential BE and biopsy-proven high-grade dysplasia or intramucosal cancer underwent EMR-C. We evaluated: (1) complete eradication of neoplasia, (2) complete eradication of metaplasia, and (3) complications including bleeding and esophageal stricture., Results: Complete eradication of neoplasia and complete eradication of metaplasia were achieved after a median follow-up of 18.4 months in 91% (43/47) of patients. After EMR-C, two patients (one IMC, one invasive cancer) underwent esophagectomy. Histology of the resected specimens showed no residual disease and a T1bN0 lesion, respectively. Two patients had progression of neoplasia. A stenosis occurred in 18 out of 45 patients (40%). All stenoses were treated with dilations and two required temporary placement of a covered stent., Conclusion: One-step complete EMR-C is a safe and effective technique which can be considered in patients with early neoplastic lesions. Although 40% of patients developed dysphagia, this could well be managed endoscopically., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers., Methods: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay., Results: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l)., Conclusions: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year., (© 2013 S. Karger AG, Basel.)

The best approach to resolve colonic obstruction in patients with left-sided colon cancer is not established. In this meta-analysis the efficacy of stenting as bridge-to-surgery was compared to emergency surgery for the management of left-sided colonic obstruction. Fourteen studies (randomized and non controlled studies) were identified, including 405 patients in the stent group and 471 in the emergency group. The difference between proportions was evaluated as effect size (ESi). There was large heterogeneity among the studies. Stenting offered advantages over emergency surgery in terms of increase in primary anastomosis (ES=25.1%, p<0.001), successful primary anastomosis (ES=23.7%, p<0.001), reduction of stoma creation (ES=-27.1%, p=0.03), infections (ES=-7.9%, p=0.006) and other morbidities (ES=-13.4%, p<0.001). The interventions were similar in regards to length of hospitalization, preoperative mortality and long-term survival., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

CYFRA 21-1 and CEA have been applied for the differential diagnosis of malignant pleural mesothelioma (MPM). The soluble mesothelin-related peptide (SMRP) has been proposed as a specific marker for distinguishing MPM from benign diseases and other malignancies in pleural effusions (PEs). In this study, we evaluated the usefulness of SMRP in PEs in the detection of mesotheliomas by comparing it with that of CYFRA 21-1, CEA, and with cytological examination. One hundred and seventy-seven consecutive patients (57 MPM, 64 metastatic tumors, and 56 benign diseases) were evaluated using commercial tests. The performance of the markers was analyzed by standard ROC analysis methods, using the area under a ROC curve (AUC) as a measure of accuracy. CYFRA 21-1 better differentiated malignant from benign effusions. The corresponding area under the receiver operating characteristic curve was 0.87, while it was 0.74 for SMRP and 0.64 for CEA (p < 0.001). Conversely, SMRP differentiated MPM from all other PEs better than both CYFRA 21-1 and CEA (AUC = 0.84, 0.76, and 0.32, respectively, p = 0.003). Low levels of CEA were associated with a MPM diagnosis. The AUC for differentiating MPM from metastases was 0.81 for SMRP, 0.61 for CYFRA 21-1, and 0.20 for CEA (p < 0.001). In cases with negative or suspicious cytology, SMRP and CYFRA 21-1 identified 36/71 and 46/66 malignant PEs (29 and 31 MPM, respectively). Only 1 MPM showed a high CEA concentration. No single marker showed the best performance in any comparison. Results suggest that SMRP could improve CYFRA 21-1 and CEA accuracy in the differential diagnosis of MPM.

The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.

Background: EMR is an effective alternative to surgery for the removal of nonampullary duodenal polyps (NADPs). Cap-assisted EMR (EMR-C) has been rarely performed in the duodenum because of the risk of perforation., Objective: To evaluate the safety and effectiveness of EMR-C for the removal of large (≥ 15 mm) NADPs., Design: Retrospective study., Setting: Tertiary-care referral center., Patients: Between 2000 and 2010, 26 consecutive patients with sporadic NADPs underwent EMR-C., Intervention: EMR with the cap technique., Main Outcome Measurements: Complete eradication of polyps, complications, and recurrence., Results: A total of 14 sessile polyps (53.8%), 7 lateral spreading type nongranular tumors (26.9%), and 5 lateral spreading type granular tumors (19.2%) were treated. The median size of lesions was 15 mm. Five lesions involved one-half of the luminal circumference. Post-EMR histologic assessment showed low-grade dysplasia in 5 patients (19.2%) and high-grade dysplasia in 18 patients (69.2%). Three patients (11.5%) had well-differentiated endocrine tumors. Complete eradication was obtained in 25 of 26 (96%) patients. No perforations occurred. Three cases of intraprocedural bleeding were managed endoscopically. Median follow-up was 6 years (range 1-10 years). Residual adenomatous tissue was observed in 3 patients in lesions of 50 mm. In one of these cases, an adenocarcinoma occurred after 8 months, which was managed surgically., Limitations: Retrospective design, single center., Conclusion: This study supports the efficacy and safety of EMR-C for removing NADPs. Regular follow-up is mandatory because of the high risk of residual or recurrent adenomatous tissue and even cancer., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.

Background: Development of graphical/visual presentations of cancer etiology caused by environmental stressors is a process that requires combining the complex biological interactions between xenobiotics in living and occupational environment with genes (gene-environment interaction) and genomic and non-genomic based disease specific mechanisms in living organisms. Traditionally, presentation of causal relationships includes the statistical association between exposure to one xenobiotic and the disease corrected for the effect of potential confounders., Methods: Within the FP6 project HENVINET, we aimed at considering together all known agents and mechanisms involved in development of selected cancer types. Selection of cancer types for causal diagrams was based on the corpus of available data and reported relative risk (RR). In constructing causal diagrams the complexity of the interactions between xenobiotics was considered a priority in the interpretation of cancer risk. Additionally, gene-environment interactions were incorporated such as polymorphisms in genes for repair and for phase I and II enzymes involved in metabolism of xenobiotics and their elimination. Information on possible age or gender susceptibility is also included. Diagrams are user friendly thanks to multistep access to information packages and the possibility of referring to related literature and a glossary of terms. Diagrams cover both chemical and physical agents (ionizing and non-ionizing radiation) and provide basic information on the strength of the association between type of exposure and cancer risk reported by human studies and supported by mechanistic studies. Causal diagrams developed within HENVINET project represent a valuable source of information for professionals working in the field of environmental health and epidemiology, and as educational material for students., Introduction: Cancer risk results from a complex interaction of environmental exposures with inherited gene polymorphisms, genetic burden collected during development and non genomic capacity of response to environmental insults. In order to adopt effective preventive measures and the associated regulatory actions, a comprehensive investigation of cancer etiology is crucial. Variations and fluctuations of cancer incidence in human populations do not necessarily reflect environmental pollution policies or population distribution of polymorphisms of genes known to be associated with increased cancer risk. Tools which may be used in such a comprehensive research, including molecular biology applied to field studies, require a methodological shift from the reductionism that has been used until recently as a basic axiom in interpretation of data. The complexity of the interactions between cells, genes and the environment, i.e. the resonance of the living matter with the environment, can be synthesized by systems biology. Within the HENVINET project such philosophy was followed in order to develop interactive causal diagrams for the investigation of cancers with possible etiology in environmental exposure., Results: Causal diagrams represent integrated knowledge and seed tool for their future development and development of similar diagrams for other environmentally related diseases such as asthma or sterility. In this paper development and application of causal diagrams for cancer are presented and discussed.

Background and Objective: Familial clusters of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have been reported. This study evaluates the history of cancer in BE patients families., Methods: In two years, patients with BE (272), esophagitis (456) and controls (517) were recruited in 12 Italian Endoscopy Units. Cancer family history in first-degree (FD) relatives was determined by a questionnaire., Results: Approximately 53% of BE, 51% of esophagitis, and 48% of controls had at least one relative affected by any type of malignancy. Probands with at least one esophageal or gastric (E/G) cancer-affected relative showed a BE risk which was at least eighty-five percent higher than that of probands without affected relatives. The relative risk of BE was 4.18, 95% CL=0.76-23.04 if a FD relative had early (mean age ≤ 50 years) onset E/G cancer compared to late onset E/G cancer., Conclusion: In this sample there was no evidence that a family history of cancer was associated with the diagnosis of BE. An intriguing result was the association between the occurrence of E/G cancers at earlier ages (< 50 years) among BE relatives with respect the control group. This could suggest a genetic contribution in onset of these tumors, but the sample was too small to demonstrate a significant association. Further exploration of family history of E/G cancer and a diagnosis of BE in larger samples is warranted., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Identification of modifiable risk factors is an attractive approach to primary prevention of esophageal adenocarcinoma (EAC) and esophagogastric junction adenocarcinoma (EGJAC). We conducted a review of the literature to investigate the association between specific dietary components and the risk of Barrett’s esophagus (BE), EAC and EGJAC, supposing diet might be a risk factor for these tumors. Consumption of meat and high-fat meals has been found positively associated with EAC and EGJAC. An inverse association with increased intake of fruit, vegetables and antioxidants has been reported but this association was not consistent across all studies reviewed. Few studies have examined the association between diet and BE. Additional research is needed to confirm the aforementioned association and clarify the mechanisms by which dietary components affect the risk of developing EAC and EGJAC. Future studies could advance our knowledge by emphasizing prospective designs to reduce recall bias, by using validated dietary intake questionnaires and biological measures and by considering important confounders such as gastro-esophageal reflux disease (GERD) symptoms, tobacco and alcohol use, biometrics, physical activity, and socioeconomic factors.

Background and Objective: An important issue in human biomonitoring is determining how exposure duration affects the kinetics of molecular biomarkers. In this study we compare the influence of exposure variables on DNA adducts., Methods: DNA adducts were analysed by 32P-postlabelling in lympho/monocytes of 677 Caucasian subjects., Results: After correction for other variables, DNA adducts increased depending on the length of occupational and smoke exposures. Higher DNA adducts were detected in workers with more than 14 years of exposure than in workers with shorter exposures (RR = 1.19, p = 0.049) and in smokers with more than 10 years of exposure than in smokers with shorter exposure (RR = 1.21, p <0.001)., Conclusions: Exposure length is the primary factor affecting DNA-adduct level in lympho/monocytes both in smokers and in occupationally exposed subjects.

Self-expanding metal stents (SEMS) are used to treat obstructive malignancies of the esophagus or esophagogastric junction; however, a potential complication is recurrent dysphagia because of tissue in/overgrowth. The placement of a second SEMS is one strategy to re-establish patency of the esophageal lumen. We evaluated the safety and efficacy of an alternative and likely less costly approach: placing a self-expanding plastic stent (SEPS) to manage relapsing dysphagia in patients previously treated with a partially covered SEMS. From December 2007 to January 2009, 13 patients previously treated with a SEMS for malignant dysphagia underwent treatment by inserting a SEPS to palliate relapsing dysphagia, as a result of tissue in/overgrowth. Stenosis was located in the upper esophagus in one patient, in the middle in four patients, and in the lower esophagus in eight patients. Clinical evaluation was performed at the time of stent placement, after 1 week, and then, monthly until death. The SEPS was successfully placed in a single treatment session for all patients. No preliminary dilation was required, and no further treatment was necessary for any patient. Before stenting, the median dysphagia score was 4 (range 3-4), and 1 week later the score was 0 for all patients. The resolution of dysphagia persisted until patient death (from tumor progression). The mean survival after the SEPS insertion was 4 months (range 3-8). This case series supports the use of a SEPS to palliate dysphagia from tissue in/overgrowth of a SEMS. Future clinical trials with larger patient samples are warranted., (© 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Standard endoscopic mucosal resection (EMR) is limited with regard to lesions below or involving the ileocecal valve. We describe the treatment and outcomes when using cap-assisted EMR (EMR-C) to remove large laterally spreading tumors (LSTs) with ileal infiltration in seven patients (median age 74 years). Each LST (median size 40 mm) was successfully resected in one session (median procedure time 50 minutes). Intraprocedural and early bleeding occurred in two patients, and delayed hemorrhage in one. Circumferential resection of the ileum caused asymptomatic strictures in six patients, with regression during follow-up for five. We conclude that the novel EMR-C method is a potentially effective treatment for cecal LST involving the distal ileum. Serious complications such as perforation or symptomatic strictures of the ileocecal valve were not observed and any procedure-related bleeding was easily controlled., ((c) Georg Thieme Verlag KG Stuttgart . New York.)

Purpose: Cap-assisted endoscopic mucosal resection has been used to treat superficial esophageal and gastric cancers. Efficacy data in the colon are limited. The aim of the study was to evaluate the safety and efficacy of this technique in the treatment of sessile polyps and lateral spreading tumors in the colorectum., Methods: Two-hundred and fifty-five consecutive patients with sessile polyps or lateral spreading tumors >or=20 mm were treated between January 2000 and December 2007., Results: A total of 146 sessile polyps and 136 lateral spreading tumors were treated with cap-assisted endoscopic mucosal resection. Complications occurred in 22 (8.6%) patients (5.5% in sessile polyps and 10.3% in lateral spreading tumors). Intraprocedural bleeding occurred in 21 (7%) of polypectomies (6% in sessile polyps and 10% in lateral spreading tumors); all were controlled endoscopically. Postcoagulation syndrome occurred in 1 patient with lateral spreading tumor. No perforation occurred. Invasive adenocarcinoma was found in 35 patients, of whom 15 underwent surgery. Endoscopic follow-up in 200 patients with 216 adenomas for a median of 12.1 months showed recurrence in 8 (4%) who were treated with resection and/or ablation., Conclusions: Cap-assisted endoscopic mucosal resection is an effective treatment for sessile polyps and lateral spreading tumors. A disadvantage of the technique is that the resection is piecemeal. Close surveillance provides the opportunity for additional tissue ablation, when required, to achieve complete lesion removal.

Background: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM., Methods: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi)., Results: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion., Conclusions: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.

Background: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate., Patients and Methods: To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients., Results: An objective response was achieved in 27 out of 65 (41.5%) patients with NSE < 8.6 ng/ml and in 38 out of 64 (59.4%) patients with NSE > or = 8.6 ng/ml (p = 0.05). Logistic analysis confirmed the positive association between objective response and NSE values > or = 8.6 ng/ml (odds ratio = 1.69; 95% confidence interval: 1.09-2.63; p = 0.02). Overall median survival was 10.8 months. A statistically significant prognostic effect on survival was found for performance status, stage and response to treatment, but not for baseline NSE value., Conclusion: Based on these data, baseline circulating tumor NSE levels appear to have a weak predictive role, but not a prognostic significance in patients with advanced NSCLC submitted to standard chemotherapy.

Objectives: Self-expanding metal stents (SEMS) provide effective palliation in patients with malignant dysphagia, although severe complications and mortality may result. We performed a prospective controlled trial to compare a new self-expanding polyester mesh stent (Polyflex) with SEMS (Ultraflex)., Methods: One hundred one patients with unresectable esophageal carcinoma were randomized to placement of a Polyflex (N=47) or a partially covered Ultraflex (N=54) stent. Patients with esophagogastric junction (EGJ) malignancy were excluded., Results: Placement was successful in 46 (98%) patients with the Polyflex and 54 (100%) patients with the Ultraflex stent. In one patient, the Polyflex stent could not be placed. After 1 wk, dysphagia was improved by at least 1 grade in 100% of the Polyflex group and in 94% of the Ultraflex group. Major complications were observed in 48% of the Polyflex group and 33% of the Ultraflex group. Intraprocedural perforation occurred in 1 Polyflex and 1 Ultraflex patient. Two Polyflex patients had postprocedural hemorrhage. Twenty (44%) patients with a Polyflex stent and 18 (33%) with an Ultraflex stent had recurrent dysphagia because of tumor overgrowth, stent migration, hyperplastic granulomatous reaction, or food bolus impaction. Multivariate analysis showed a significantly higher complication rate with Polyflex than with Ultraflex stents (odds ratio 2.3, 95% CI 1.2-4.4). However, median survival was 134 days with Polyflex and 122 days with Ultraflex stents (P=NS)., Conclusions: No difference was seen in palliation of dysphagia between the two stents. Significantly more complications, especially late stent migration, were observed in the Polyflex group.

Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled., Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker., Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM., Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.

Adenomas of the duodenum have been described in patients with familial adenomatous polyposis (FAP). Patients with FAP are at high risk for the development of periampullary cancer. The aim of our study was to evaluate if endoscopic visualization of small polyps, often overlooked at standard endoscopic examination, was improved by chromoendoscopy. Ten patients with FAP and previous colectomy underwent upper gastrointestinal endoscopy. Two skilled endoscopists were involved for each endoscopy. Evaluation of number and diameter of polyps was made before and after staining. After staining we detected a larger number of duodenal polyps than found at the standard endoscopic examination, the difference being statistically significant. This result seems to suggest that chromoendoscopy may improve diagnostic yield of endoscopy. Further studies are needed to suggest the best surveillance program and the appropriate therapeutic modality for these patients.

High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).

Pleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.

Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.

Background: The management of patients with refractory hypopharyngeal strictures after surgery in combination with radiation therapy is disappointing, and nutrition through feeding tubes is often required., Objective: To evaluate the efficacy and safety of a modified self-expanding Niti-S metal stent in the treatment of hypopharyngeal strictures after combined therapy for laryngeal cancer., Design: Case series., Setting: A general hospital and a university hospital., Patients: Seven consecutive patients were included. One of them did not have laryngectomy., Interventions: All patients received a modified Niti-S stent., Main Outcome Measurements: Improvement of dysphagia, avoiding periodic bougienage, and enteral nutrition through feeding tubes., Results: After placement of the first stent, dysphagia improved in all patients. Six of 7 patients developed stent migration and/or granulomatous tissue ingrowth or overgrowth. Additional stents were placed in all patients after a median of 3 months after the previous stent placement. One patient developed an esophagorespiratory fistula caused by a Polyflex stent. Two patients died of causes unrelated to the stent. The remaining 5 patients remained alive and asymptomatic after a median follow-up of 10 months., Limitations: Periodic stent exchange. Stent placement did not resolve the stricture definitively. We had a limited number of patients and have no long-term outcome data yet., Conclusions: The use of this modified Niti-S stent avoids both enteral nutrition through feeding tubes and the need for periodic bougienage in patients with difficult-to-treat benign hypopharyngeal strictures.

Objective: Dysphagia is the most distressing symptom in patients with cancer-related oesophageal obstruction. Endoscopic palliation aims to restore swallowing, avoid reintervention and to reduce hospitalization. This study reports an experience with a new self-expandable plastic stent (Polyflex) in patients with unresectable oesophageal and oesophagogastric junction cancer., Methods: Sixty patients were prospectively collected. The cause of obstruction was oesophageal squamous cell carcinoma (44) and adenocarcinoma (eight), lung cancer (seven) and thyroid tumour (one)., Results: The stent was successfully placed in 59 patients. Early minor complications occurred in 19 patients (32%), and major complications in 13 (22%). Death occurred in three patients owing to pulmonary embolism (one) and massive haemorrhage (two). Recurrent dysphagia for early stent migration was observed in seven patients. Delayed stent migration occurred in five patients and tumour overgrowth in eight patients. The mean dysphagia score of 2.8 improved to a mean score of 1.0 after stenting (P<0.001). Overall median survival time was 4.6 months., Conclusions: Our study suggests that Polyflex stents are competitive with metal stents, with similar efficacy but lower cost. Technical improvements, however, are required to make these stents more user friendly. Large randomized clinical studies are needed to guide in the choice among the different available stents.

Background: The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC)., Methods: Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival., Results: One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (> or =20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival., Conclusions: CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC., (Copyright 2006 American Cancer Society.)

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.